Nutritional composition

ABSTRACT

A nutritional composition having a total energy content of 67 kcal/100 ml or lower and including: a protein content which is 1.25 g/100 ml or lower, an energy content from protein of 7.2-8.4% of the total energy content of the nutritional composition, an energy content from fat which is at least 49% or more of the total energy content of the nutritional composition, a medium chain fatty acid content comprising 8 to 10 carbons which is less than 3 wt % of total amount of fatty acids, a sialic acid content of 10-25 mg/100 ml, a cholesterol content of 5-10 mg/100 ml, and a sphingomyelin content of 9-15 mg/100 ml is disclosed.

RELATED APPLICATION DATA

This application is a continuation application of pending prior U.S.patent application Ser. No. 14/391,494, filed Oct. 9, 2014, which is theNational Stage of International Application No. PCT/EP2013/057405 filedApr. 9, 2013, and claims benefit of Swedish Application No. 1250357-9filed Apr. 10, 2012, which are all herein incorporated by reference intheir entirety.

FIELD OF INVENTION

The present invention concerns the field of nutritional compositions andinfant formulas.

BACKGROUND

Research has shown that birth weight and growth patterns during thefirst years of life are relevant to the development of the metabolicsyndrome with obesity, insulin resistance, type 2 diabetes and increasedrisk of cardiovascular disease in adulthood (D. J. P. Barker. HormoneResearch 2005; 64 (suppl. 3):2-7). According to “the growth accelerationhypothesis” a fast growth during the first year of life, probably due toimprinting effects on the metabolic system in the body, results in anincreased risk to develop metabolic syndrome, type-2 diabetes andcoronary heart diseases later in life. (A. Singhal et al. The Lancet,2004, vol. 363: 1642-1645).

Formula-fed infants put on weight faster during the first year of lifecompared to breastfed infants (J. Baird et al. Paediatric and PerinatalEpidemiology, 2008, Vol. 22, 575-586. K. G. Dewey. Biol Neonate, 1998;74:94-105).

Infants who are formula-fed have in adulthood increased risk of impairedglucose tolerance and unfavourable lipid profile with lowHDL-cholesterol and high LDL-cholesterol, all known risk factors forcardiovascular disease (A. C. J. Ravelli et al. Arch Dis Child 2000;82:248-252). If the infant formula is made more like human milk this maypossibly give a reduction of these differences and, it could provide asubstantial reduction of morbidity in the population.

Infant formula is commonly based on cow's milk proteins, which differfrom breast milk proteins in their amino acid composition. To coverinfant's needs of amino acids the protein level in the infant formulatherefore has to be higher. This gives a much higher total intake ofprotein by formula-fed infants, which can give a metabolic stress on theinfants.

Koletzko B et al. suggest that limiting the protein content of infantand follow-on formula and, more generally, the dietary protein intakeduring infancy might constitute a potentially important approach toreducing the risk of childhood overweight and obesity. A largerandomized controlled trial showed significant effects of a lowerprotein intake from infant formula on weight, weight-for-length, and BMIduring the first 2 years of life. (B. Koletzko et al. Am J Clin Nutr,2009; 89:1836-1845).

Increased protein intake as is the result of using the high proteinformulas out on the market today leads to higher insulin levels in theinfants. Formula-fed infants get about 70% more protein than breastfedinfants between 3-6 months of age (M. J. Heinig et al. Am J Clin Nutr,1993; 58:152-156). More figures regarding increased protein intake arealso shown in a more recent European study. (Koletzko B. et al, Adv ExpMed Biol. 2005; 569:69-79).

Infant formula fed children also have a higher energy intake thanbreastfed children. The reason why formula-fed children have a higherrisk of getting too much energy relative to their need to meet theirgrowth is multifactorial. Mothers who give food in the bottle have agreater tendency to “maternal control”, i.e. the child is less able tocontrol its own intake, compared with breastfed children (T. E. M.Taveras et al. Pediatrics, 2004, vol. 114 (5) e577-e584).

In a study of cholesterol intake by Demmers T. A. et al. the formula-fedinfants had at 4 months of age 40% higher energy intake than thebreastfed infants. (T. A. Demmers et al. Pediatrics, 2005, vol. 115 (6)1594-1601). Increased “maternal control” has been shown to accelerateoverweight among heavy children and also to increase the problem withunderweight among children with difficulties to put on weight (C. Farrowet al. Pediatrics, 2006, vol. 118 (2) e293-e298).

Infants fed with different formulas with different energy densityappeared able to compensate to some extent for greater or lesser energydensity by adjusting the quantity of food consumed, but a higher energydensity of the formula tends to increase the calorie intake of theinfant (S. J. Fomon et al. J. Nutrition, 1969, 98: 241-254 and S. J.Fomon et al. Acta Paediatr Scand 64: 172-181, 1975). There is a biginterest in these issues but only a few studies available.

There are differences seen in morbidity between breastfed andformula-fed infants. Breastfed infants have less respiratory infections,ear infections and gastroenteritis than formula-fed infants. (A. L.Wright et al. BMJ, vol. 299, 946-949, B. Duncan et al. Pediatrics, 2003,vol. 91 (5) 867-873, G. Aniansson et al. Pediatr Infect Dis J, 1994,vol. 13 (3) 182-188 and K. G. Dewey et al. J Pediatr, 1992, vol. 126(No. 5) part 1 695-702). One possible explanation is that breast milkcontains more immune modulating substances than cow's milk.

Sialic acid is found in milk both bound to proteins, e.g. kappa-caseinwith its content of glyco macro peptide (cGMP), and lipid bound ingangliosides. Sialic acid is found in high concentrations in human brainand breast milk, and has been proposed as a milk factor that could havean impact on the development of the central nervous system (B. Wang etal. Eur J Clin Nutr, (2003) 57, 1351-1369). Enrichment of sialic acid inthe diet of piglets has been shown to improve memory and learning (B.Wang et al. Am J Clin Nutr, 2007; 85:561-569).

Furthermore, long-chain polyunsaturated fatty acids (LCPUFA) have aclear impact on the developing nervous system. Breastfed children havehigher levels of arachidonic acid (ARA) and docosahexaenoic acid (DHA)in both blood and brain than children who received formula without theaddition of ARA and DHA (M. Makrides et al. Am J, Clin Nutr 1994;60:189-94).

Dietary sphingomyelin is probably also important for the development ofan infant's nervous system. In studies with rat it is shown thatenrichment with sphingomyelin in the diet increases the myelisation ofthe nervous system (K. S. T. Oshida et al. Pediatr Res, 2003. 53: p.589-593). Breast milk contains sphingomyelin and the amount is between4-9 mg/100 g.

Using new technology within the milk industry, purification enables newfractions of milk to be separated. An example of such a fraction is“milk fat globule membrane” (MFGM), which comprises 120 differentproteins in a phospholipidic double layer which surrounds fat dropletswithin the milk. Sphingomyelin, phosphatidyl choline, phosphatidylserine and phosphatidyl ethanolamine are the dominating phospholipids.Butyrophilin, MUC1 and PAS6/7 (lactadherin), CD14, TLR1 and TLR4 areexamples of the dominant proteins which all have antimicrobiologicaleffect (V. L. Spitsberg. J Dairy Sci, 2005. 88: p. 2289-2294, T. A.Reinhardt & J. D. Lippolis. J Dairy Res, 2006. 73(4): p. 406-416).

The cholesterol level in breast milk is much higher than in a regularvegetable oil based infant formula. The level in breast milk is around10 mg/100 ml and the level in infant formulas on the market is around0.2-1.0 mg/100 ml. Therefore breastfed infants today get a much higherintake of cholesterol than formula-fed infants. This gives a higherblood cholesterol level in breastfed infants during infancy. However atolder age, >17 years, breastfed infants show a lower blood cholesterollevel, which is associated with lower risk for development ofcardiovascular disease compared to children who were formula-fed (C. G.Owen et al. Am J Clin Nutr, 2008; 88:305-314, T. A. Demmers et al.Pediatrics, 2005, vol. 115 (6) 1594-1601). The blood cholesterol levelin infants is not only dependent on the oral intake of cholesterol, butalso of the endogenous synthetic rate of cholesterol. Studies on infantshave shown that formula-fed infants, who have a low blood cholesterollevel, have an up regulated endogenous synthetic rate of cholesterol, incomparison with breastfed infants. Maybe this is an effort to try tocompensate for the low oral intake. In spite of this endogenous upregulation of cholesterol synthesis, formula-fed infants have a lowerlevel of blood cholesterol than breastfed infants. Efforts havetherefore been made to add cholesterol to infant formula to mimic thelevel in breast milk and increase the blood level of cholesterol informula-fed infants (T. M. Bayley et al. Metabolism 2002; 51:25-33). Toshed further light on this Demmers et al. performed a clinical study oninfants, where cholesterol was added to infant formula as solved inethanol to increase the availability. Blood cholesterol and FSR(fractional synthesis rate) were analysed up to 18 months of age. Theydemonstrated decreased cholesterogenesis and increasing circulatingplasma cholesterol concentration at 4 months of age as the dietarycholesterol increased. But these differences were not seen at 18 monthsof age. The ratio of total cholesterol/HDL-cholesterol differed betweenbreastfed and cholesterol supplemented cow's milk formula group at 4months which indicates a different cholesterol metabolism betweenbreastfed and cholesterol supplemented group. Since the study group wasonly followed up to 18 months the long term consequences of this is notknown. Although the results confirmed the results from other studiesthat an increased cholesterol intake during the first months gives ahigher total blood cholesterol level, both the importance of how thecholesterol is added and the long term consequences on cholesterol levelat adulthood have to be further studied. (T. A. Demmers et al.Pediatrics, 2005, vol. 115 (6) 1594-1601).

Specific Background

There is a need for a nutritional composition or an infant formula whichgives the formula-fed infant for example a growth pattern, metabolicburden and level of blood cholesterol similar to breastfed children andalso at the same time for example reduces risk of morbidity duringinfancy as well as later in life.

There is also a need for a production method for such a nutritionalcomposition which has all the desired ingredients in order to achieve anutritional composition which gives the nutritional compositionformula-fed infants a similar growth and development pattern asbreastfed children. There is also at the same time need of a productionmethod to produce a nutritional composition which allows for a goodtaste for such a nutritional composition, for example similar to thetaste of breast milk.

There is a need to develop an infant formula with reduced proteincontent and low energy content, which still covers the infant's need ofamino acids and other nutrients.

PRIOR ART

None of the prior art discloses a nutritional composition according tothe invention;

Several attempts of making an infant formula more like human milk havebeen performed:

Methods for producing low protein and high calorie content formulas areshown in EP1841330B1. However the method described in EP1841330B1 doesnot include a method for producing a formula with increased level ofsialic acid and cholesterol and it is not a formula with reduced energy.In US 2008003330 a method to make a formula with increased level ofsialic acid and phospholipids is disclosed, but with a standard highlevel of proteins as well as a standard level of energy and cholesterol.The infant formula described in US2008003330 uses MFGM additions.

WO2007073192 shows an infant formula depleted fromcasein-glyco-macropeptide (cGMP).

Infant formulas with increased concentrations of α-lactalbumin have alsobeen presented in order to mimic breast milk composition but with astandard high level of proteins and energy (for example; E. L. Lien. AmJ Clin Nutr, 2003; 77 (suppl):1555S-1558S). The objective of thedescribed study was to study the effects of glyco macro peptide- orα-lactalbumin-supplemented infant formulas on growth, mineral status,iron-, zinc- and calcium absorption, as well as plasma amino acids,blood urea nitrogen and plasma insulin concentrations. Breastfed infantsand infants fed with α-lactalbumin enriched formula had similar plasmaessential amino acid and insulin profiles, which were different fromthose of infants fed with glyco macro peptide or control formula.

WO 2010/027258 A1 shows an infant formula comprising a lipid componentwhich has a larger lipid globule size and wherein the protein source forexample is based on acid whey or sweet whey from whichcasein-glyco-macropeptide (cGMP) has been removed. The infant formula inWO 2010/027258 A1 preferably has a protein content of 1.25-1.35 g/100ml.

In previous developed infant formulas, the cGMP content in the infantformulas was lowered to reduce the amount of threonine (see for exampleWO2006069918, page 4).

OBJECT OF THE INVENTION

The general object of the invention is to find a new nutritionalcomposition, for example an infant formula or a follow on formula whichresults in the same or similar growth and development and morbidity asfor breastfed children within the first months in an infant's life butalso the same growth and development later in life when the infants orchildren become grown-ups. There is a need for a nutritional compositionwhich results in growth and development of formula-fed infants in asimilar manner as breastfed children and which still doesn't unnecessaryburden the infants' metabolic and renal systems and which also issimilar in taste as breast milk. There is also a need for a productionmethod for producing such a nutritional composition.

SUMMARY OF THE INVENTION

Infant formulas are for example intended to be used as the only dietarysource for infants that are not breastfed or as a supplement topartially breastfed infants or as a part of the diet after weaning. Tobe able to fulfil this, the product has to cover many different dietaryrequirements of the infant. It was therefore a great challenge toformulate an adequate nutritional composition according to theinvention.

The challenges known to the skilled person, but not at presentsatisfactory taken care of are: protein content and protein quality,energy density, content of essential fatty acids, content of mediumchain fatty acids (MCT), content of sialic acid, gangliosides,sphingomyelin, and the content and quality of cholesterol in theformulas out on the market today. According to the present invention ithas surprisingly been possible to improve all these parameters withoutat the same time negatively affect the overall composition of theproduct.

Protein quantity and protein quality: There shall be an adequate amountof protein, but not too high level (as referred to above) and theprotein quality must be such that it is well digested by the infant andwill cover the amino acid requirement of the infant in as low quantityof protein as possible. Since the amino acid requirement absolutely mustbe covered one has earlier been forced to add an excess of protein dueto the composition of the protein sources used. There was therefore aneed to invent a product that within a lower protein level can cover theamino acid requirement. At the same time it is important to keep thenon-protein nitrogen (NPN) at a low level. All this is achieved with thenutritional composition and the production method according to thepresent invention.

Energy density: It is well known that infants fed a standard formulashow a more rapid weight gain than breastfed infants. This is due toseveral factors: A higher protein intake, a higher caloric intake due toa higher energy density of the formula and a less developedself-regulation of caloric and volume intake. Since a part of the totalcarbohydrates in breast milk (the oligosaccharides) are not used as anenergy source and the lactose content in infant formula earlier wasregarded as the same as the total carbohydrate content in breast milk.The content of lactose in the nutritional composition according to theinvention is reduced in order to reach a nutritional composition withdecreased energy density (kcal/100 ml). No one has before developed aproduct where both protein content and caloric content are reduced whichstill has all other nutrients present in desired levels. According tothe present invention such a formula has been developed. The nutritionalcomposition according to the invention has been tested in a clinicalstudy. The growth of the infants using the nutritional compositionaccording to the invention was similar to the growth of breastfedinfants. The study thereby shows that the content of energy and aminoacids was satisfactory.

Phospholipids, sphingomyelin, sialic acid, gangliosides are allnutrients which are recognized as important nutrients for the infant.The challenge has been to be able to incorporate suitable sources ofthese nutrients into the composition of the formula without negativeeffect on other important nutrients and the general composition of theproduct. In the present invention this incorporation has been performedin levels close to the level in breast milk without any negative effecton the total composition.

Cholesterol is also recognized as an important component in infantformula. However, so far, a method to include available cholesterol inthe product in such a manner that it is well absorbed and metabolizedhas not been developed. Addition of free cholesterol has been tested inprevious studies, but there are questions about its availability,metabolism and protection against oxidation during processing. In thepresent invention this has been solved by addition of cholesterol richraw materials, without negative effect on other important parameters.

Other important ingredients as essential fatty acids, long chain polyunsaturated fatty acids, medium chain triglycerides, minerals, vitaminshave all been added as carefully selected raw materials.

The result of the invention is a formula where the above mentionedchallenges have all been possible to fulfill simultaneously, withoutcompromising with ingredients in the general composition of the product.A clinical study with a formula according to the invention has beenperformed. The result verifies the goal of the invention. The overallaim with the nutritional composition for example an infant formulaaccording to the invention is to reach an outcome similar to breastfedinfants with regard to development of infants fed with the compositionaccording to the invention rather than to reach an infant formula whichhas ingredients present in similar levels as in breast milk.

The production method according to the invention; i.e. the carefulselection of ingredients present in the described amounts according tothe invention is not an obvious selection to a person skilled in theart. Surprisingly the selection of ingredients at the present levelsaccording to the invention makes the formula both fulfil the nutritionalrequirements of the authorities and at the same time, due to the specialcomposition selection, makes infants fed with the nutritionalcomposition according to the invention behave and develop more likebreastfed infants. Finding a nutritional composition which makes theinfant, fed with the formula behave and develop similar to infants fedwith breast milk is a known problem which until now has remainedunsolved. A nutritional composition is invented which has a low proteincontent as well as low energy content and this is combined with a highcontent of milk derived phospholipids and sialic acid and cholesteroland further in combination with no addition of free amino acids. Theformula according to the invention has a low protein content, expressedin g/100 ml, which still gives a low energy percentage (E %) derivedfrom proteins compared to standard formula in spite of the reducedenergy content of the formula.

This nutritionally complete formula will contribute to that thedevelopment of the child regarding growth, body composition, metabolicparameters, morbidity and neurological development becomes more similarto that of breastfed children.

Parameters which are influenced when using the formula according to theinvention are for example growth, body composition (% fat), bloodcholesterol, blood urea nitrogen (BUN), sialic acid in saliva, fastinginsulin, blood pressure, morbidity short term, immunological parameters,neurological parameters and micro flora. Long term parameters are forexample decreased obesity and morbidity in childhood as well asadulthood. The infants fed with the nutritional composition according tothe invention surprisingly develop in a manner closer to breast-fedinfants' development.

A nutritional composition according to the invention fulfils theobjectives of making the infant fed with the composition to grow anddevelop in the same manner as breastfed infants.

Use of the nutritional composition during the first 6 months of life ofan infant as the only nutrition, or from birth to up to 12 months of ageas a complementary diet may for example minimize the difference ingrowth and/or body composition (weight (wt) % fat) and/or cholesterollevels and/or blood urea nitrogen values and/or plasma amino acidsand/or sialic acid in saliva and/or fasting insulin levels and/ormorbidity and/or inflammation parameters and/or occurrence of obesity inchildhood between breastfed and formula-fed children in combination withthat the nutritional composition according to the invention gives nounnecessary burden to the metabolic system of the formula-fed infants.

Previously infant formulas were made using whey protein concentrate fromwhich the cGMP was removed. This is for example described in EP 2046149.Surprisingly, due to the special selection of ingredients present in thecomposition according to the invention, cGMP does not have to be removedand this facilitates for presence of high sialic acid levels in thenutritional composition according to the invention. In the formulaaccording to the invention the threonine content is not too high. Theamino acid levels in the invention formula are in line with the limitsset up by the government Commission Directive 2006/141/EC and still theformula also is within limits for protein and energy content as set upaccording to the directive. No one has previously produced a formulawith both low protein and low energy content, which in combination withthis has high sialic acid content and high content of milk derivedcholesterol. There is nothing in the literature that would instruct theperson skilled in the art how to produce such a formula. Since there arethat many different parameters which have to be considered it is notobvious how to compose an infant formula which fulfils the need of theinfants as well as the commission directive, national legislations andrecommendations within the paediatric nutritional field.

The purpose of the invention is not to be as close as possible incomposition as breast milk, but to be as close as possible in outcomefor the infants fed with the formula according to the invention. Uptakeand availability of nutrients are different from the formula compared tobreast milk.

The infants have a growth and development more similar to breastfedinfants when they are fed with the formula according to the invention.

Below different embodiments according to the invention are shown, theembodiments are exemplifying embodiments and not limiting the scope ofthe invention:

In one embodiment of the invention the nutritional composition accordingto the invention comprises;

-   -   a total energy content of 67 kcal/100 ml or lower, for example        62 kcal/100 ml or lower, especially lower than 60 kcal/100 ml or        between 58-62 kcal/100 ml or for example 58-60 kcal/100 ml    -   a protein content of 1.25 g/100 ml or lower, or for example        lower than 1.25 g/100 ml or for example between 1.1-1.25 g/100        ml or between 1.1 g/100 ml to lower than 1.25 g/100 ml.

In one embodiment of the invention the nutritional composition accordingto the invention has a total energy content of 62 kcal/100 ml or lowerand the composition comprises;

-   -   a protein content which is 1.25 g/100 ml or lower,    -   a cholesterol content of 5-10 mg/100 ml.

In one embodiment of the invention the nutritional composition accordingto the invention has a total energy content of 62 kcal/100 ml or lowerand the composition comprises;

-   -   a protein content which is 1.25 g/100 ml or lower,    -   an energy content from protein of 7.8-8.4 percent of the total        energy content of the nutritional composition,    -   an energy content from fat which is at least 49 percent or more        of the total energy content of the nutritional composition,    -   a medium chain fatty acid comprising 8 to 10 carbons content        which is less than 3 weight % of total amount of fatty acids,    -   a sialic acid content of 10-25 mg/100 ml or higher,    -   a cholesterol content of 5-10 mg/100 ml    -   a sphingomyelin content of 9-15 mg/100 ml or higher

In another embodiment of the invention the nutritional compositionaccording to the invention comprises;

-   -   a total energy content of 62 kcal/100 ml or lower, or for        example lower than 60 kcal/100 ml or between 58-62 kcal/100 ml        or for example 58-60 kcal/100 ml    -   a protein content of 1.25 g/100 ml or lower, or for example        lower than 1.25 g/100 ml or for example between 1.1-1.25 g/100        ml or between 1.1 g/100 ml to lower than 1.25 g/100 ml.    -   an energy content from protein of 7.8-8.4 percent of the total        energy content of the nutritional composition or for example        8.0-8.3 percent of the total energy content of the nutritional        composition    -   a fat content which is at least 49 percent or more of the total        energy content of the nutritional composition or especially 50        percent or more for example 52-53 E % fat, for example 52.5% of        the energy of the formula is derived from fat    -   a medium chain fatty acid comprising 8 to 10 carbons content        which is 0.5-3 wt % of total amount of fatty acids or for        example 1-3% or for example 1-2% of total amount fatty acids in        the composition.    -   sialic acid content of 18 mg/100 ml or higher, or between 18-25        mg/100 ml    -   a sphingomyelin content of 9-15 mg/100 ml or more than 10 mg/100        ml or especially 13 mg/100 ml    -   a cholesterol content of between 5-10 mg/100 ml or between 7-10        mg/100 ml or for example 0.2-0.3 weight % of cholesterol        expressed as percentage of total fat content of the formula or        for example 8 mg/100 ml which is 0.23 wt % cholesterol expressed        as percentage of total fat content of the formula.

In another embodiment of the invention the nutritional compositionaccording to the invention further comprises

-   -   lipid bound sialic acid as gangliosides of between 1.5-5 wt % of        total sialic acid content, or for example 4 wt % lipid bound        sialic acid of total sialic acid content.

In one embodiment of the invention the energy content in the nutritionalcomposition according to the invention is for example 58-60 kcal/100 ml,wherein 51.8-53.4 E % fat. The protein content is for example 1.1-1.25g/100 ml and 7.8-8.2 E % protein, and a low NPN content, is for examplea NPN content between 0.015-0.020 g/100 ml and a high sialic acidcontent is for example 18-20 mg/100 ml. The level of milk derivedcholesterol is for example 7-9 mg/100 ml.

In another embodiment of the invention the energy content in thenutritional composition according to the invention is 60 kcal/100 ml andthe composition comprises 52.5 E % fat. The protein content is 1.2 g/100ml and the composition comprises 8 E % protein. In another embodiment ofthe invention the energy content in the nutritional compositionaccording to the invention is 60 kcal/100 ml and 52.5 E % fat, theprotein content is for example 1.2 g/100 ml and the compositioncomprises 8 E % protein, with non-protein-nitrogen (NPN) content of0.015-0.020 g/100 ml or for example 0.016 g/100 ml and 13 mg/100 ml ofsphingomyelin and a high sialic acid content is for example 19 g/100 ml.The level of milk derived cholesterol is for example 8 mg/100 ml and thecomposition comprises a medium chain fatty acid (comprising 8 to 10carbons) content which is less than 3 wt % of total amount of fattyacids

A nutritional composition according to the invention, or the useaccording to the invention, may also refer to the composition of theinvention as a powder suitable for making a liquid composition afterreconstitution with water.

The nutritional composition according to the invention may be preparedfrom powder by mixing 114 g of a nutritional composition powder with 900ml water to make 1000 ml of liquid composition according to theinvention.

The nutritional composition according to the invention further comprisesthe following features in any combination;

In other embodiments according to the invention the formula comprises5-6 wt % whey protein concentrate solids rich in phospholipids and 12-15wt % cream solids expressed as percentage of the total weight of thesolids in the composition.

In one embodiment according to the invention the formula furthercomprises a sphingomyelin content in the formula is for example between9-15 mg/100 ml, or 10 mg/100 ml or higher for example 13 mg/100 ml.

Further embodiments are also alternative embodiments according to theinvention;

A nutritional composition according to the present invention wherein thecomposition comprises intact or partly hydrolysed milk protein.

A nutritional composition according to the present invention wherein theamino acid content in the composition is originated from sourcesselected from for example; sweet whey solids, casein solids, milk solidsand cream solids.

A nutritional composition according to the present invention wherein thesphingomyelin content in the composition according to the invention isbetween 9-15 mg/100 ml, or 10 mg/100 ml or higher, especially 13 mg/100ml.

A nutritional composition according to the present invention wherein thecomposition is comprised from the following raw materials;

-   -   sweet whey solids 32-40 kg/1000 kg dry powder composition or        between 32.6-39.9 kg/1000 kg dry powder composition    -   sodium caseinate between 4.6-5.7 kg/1000 kg dry powder        composition or between 4.66-5.69 kg/1000 kg dry powder        composition    -   skim milk solids between 66-81 kg/1000 kg dry powder composition        or between 66.3-81 kg/1000 kg dry powder composition    -   whey protein concentrate solids rich in phospholipids between        47-58 kg/1000 kg dry powder composition or between 47.1-57.6        kg/1000 kg dry powder composition    -   cream solids between 117-143 kg/1000 kg dry powder composition.

A nutritional composition according to the present invention wherein thecomposition comprises; sweet whey solids of 36.3 kg/1000 kg dry powdercomposition, sodium caseinate of 5.18 kg/1000 kg dry powder composition,skim milk solids of 73.7 kg/1000 kg dry powder composition, whey proteinconcentrate solids of 52.4 kg/1000 kg dry powder composition, creamsolids of 130 kg/1000 kg dry powder composition.

A nutritional composition according to the present invention wherein thevalues described above defining the ingredients in the composition inkg/1000 kg powder is the same when defining the ingredients in thecomposition by kg/8770 L of ready to drink nutritional composition.

Further the composition may comprise vitamins (see for example vitaminsmentioned in Formula A below), minerals (see for example mineralsmentioned in Formula A below), fats (see for example fats mentioned inFormula A below or in the detailed description), lactose and/or otheressential nutrients (for example choline, taurine, inositol, carnitine,fructo oligo saccharides (FOS), galacto oligo saccharides (GOS),probiotics or nucleotides).

Further, the nutritional composition according to the invention maycomprise smaller amounts of other ingredients, for example less than 7wt % of the total formula weight. Examples of such other ingredients areother milk solids (not in specified formula) e.g. acid whey proteinconcentrate, butter milk solids, whole milk solids etc. Said otheringredients may be present as long as the specification of thenutritional composition, described above of the invention is fulfilled.

A nutritional composition according to the present invention wherein thecomposition comprises; sweet whey solids of 36.3 kg/1000 kg dry powdercomposition, sodium caseinate of 5.18 kg/1000 kg dry powder composition,skim milk solids of 73.7 kg/1000 kg dry powder composition, whey proteinconcentrate solids rich in phospholipids of 52.4 kg/1000 kg dry powdercomposition, cream solids of 130 kg/1000 kg dry powder composition.Further the composition may comprise vitamins (see for example vitaminsmentioned in Formula A below), minerals (see for example mineralsmentioned in Formula A below), fats (see for example fats mentioned inFormula A below), lactose and/or other essential nutrients (for examplecholine, taurine, inositol, carnitine).

Further, the nutritional composition according to the invention maycomprise other ingredients as long as the specification of thenutritional composition, described above of the invention is fulfilled.

Use of a composition according to the present invention as a nutritionalcomposition or as an infant formula or as a follow-on formula.

Use of a nutritional composition according to the present invention asan nutritional composition for achieving a development and/or growthpattern and/or morbidity more similar to breast-fed infants and/orregarding parameters which is any of growth, body composition wt % fat,cholesterol level, blood urea nitrogen (BUN), sialic acid in saliva,fasting insulin levels or decreased obesity and or morbidity inchildhood.

Further the production method of the invention is described according tothe following embodiments;

A method for producing a nutritional composition according to thepresent invention in order to get a high sialic acid content and a highcholesterol content in combination with low protein and energy content,comprising the steps;

-   -   providing ingredients per 1000 kg dry powder or per 8770 L ready        to drink nutritional composition;    -   sweet whey solids between 32-40 kg/1000 kg dry powder        composition or per 8770 L ready to drink nutritional composition    -   sodium caseinate between 4.6-5.7 kg/1000 kg dry powder        composition or per 8770 L ready to drink nutritional composition    -   skim milk solids between 66-81 kg/1000 kg dry powder composition        or per 8770 L ready to drink nutritional composition    -   whey protein concentrate solids rich in phospholipids between        47-58 kg/1000 kg dry powder composition or per 8770 L ready to        drink nutritional composition    -   cream solids between 117-143 kg/1000 kg dry powder composition        or per 8770 L ready to drink nutritional composition    -   Further additionally comprising for example vitamins, minerals,        fats, lactose and other essential nutrients (for example        choline, taurine, inositol, carnitine); and,    -   mixing the ingredients.

A method for producing a nutritional composition according to theinvention wherein no free amino acids are added other than naturallyoccurring free amino acids present in milk raw materials.

It is further possible to add small amounts of other ingredients intothe composition according to the invention as long as the specificationof the nutritional composition, described above of the invention isfulfilled. For example, acid whey solids can be used.

A method according to the present invention for producing a nutritionalcomposition according to the invention wherein no free amino acids areadded other than the additions made by adding raw materials from sourcesselected from; sweet whey solids, casein solids, milk solids and creamsolids.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a graph illustrating the mean weight-for-age (z-scores) by agefor the groups of Formula A (FA), control formula (CF), and breast-fed(BF) groups.

FIG. 2 is a graph illustrating the mean length-for-age (z-scores) by agefor the groups of Formula A (FA), control formula (CF), and breast-fed(BF) groups.

FIG. 3 is a graph illustrating the mean head circumference-for-age(z-scores) by age for the groups of Formula A (FA), control formula(CF), and breast-fed (BF) groups.

FIG. 4 is a graph illustrating the mean body mass index (BMI)-for-age(z-scores) by age for the groups of Formula A (FA), control formula(CF), and breast-fed (BF) groups.

DETAILED DESCRIPTION Introduction

The general object of the invention is to find a nutritionalcomposition, for example an infant formula which generates growth anddevelopment, in short and long term, in formula-fed children similar tobreastfed children.

The growth and development for the infants fed with the nutritionalcomposition according to the invention is similar to the growth anddevelopment in short and long time as for breastfed children and thiswithout unnecessary burden on the metabolic system of the infants due tooverload of nitrogen sources, for example protein in too high amounts.

A nutritional composition according to the invention is for example aninfant formula which is defined as foodstuff intended for particularnutritional use by infants from birth and during the first 6 months oflife and satisfying by itself the nutritional requirements of thiscategory of persons. Further, for example the nutritional compositionaccording to the invention may be intended to be used as a follow-onformula which is defined as a complement or as a part of a progressivelydiversified diet wherein the formula feeding starts for example when theinfant is at the age of 4 months and then the feeding of formula is apart of the infant diet up to the infant is 12 months of age. The infantmay start to include the formula according to the invention between theage of 4-6 months which is the time when most infants start with solids,or at least when the breastfed infants nutrient intake is complementedwith solids from 6 months of life up to 12 month of life. A nutritionalcomposition according to the invention may for example be an infantformula or a follow-on formula. The nutritional composition according tothe invention may also be abbreviated to as “a formula” or “acomposition”. An infant formula is a formula intended to be used as theonly source of nutrients from birth and up to 6 months of age and afollow-on formula may be defined as a formula intended to be used from 6months onwards during the weaning period, as a-complement to the solidswhich are introduced in the infant's diet at the same age.

A nutritional composition also referred to as a formula according to theinvention is for example a powder intended to be mixed with water beforeuse or a liquid ready-to-use product.

The term “ready-to-use product” as used herein, unless otherwisespecified, refers to liquid formulas suitable for direct oraladministration to an infant, wherein the formulas are ready to-feedliquids, reconstituted powders, or diluted concentrates.

Definition of an infant is a child under the age of 12 months.

The solution to the problem stated above is a nutritional compositionaccording to the invention which minimizes the difference in growth andinsulin levels between breastfed children and formula-fed children.

A nutritional composition according to the invention has low energycontent in combination with low protein content. A nutritionalcomposition according to the invention is more nutritional complete andcomprises several milk derived raw materials including sweet whey, wheyprotein concentrate rich in phospholipids, cream rich in cholesterol andalso comprises gluco macro peptide (cGMP) which allows for a highersialic acid content. Another important factor of the present inventionis that it further may have low non-protein nitrogen content (NPN).

There are several reasons for why formula-fed children have a higherrisk of getting too much energy relative to the need for their growth.Increased protein intake leads to higher insulin levels and formula-fedinfants get about 70% more protein than breast-fed infants between 3-6months of age (M. J. Heinig et al. Am J Clin Nutr, 1993; 58:152-156).(B. Koletzko et al. Am J Clin Nutr, 2009; 89: 1836-1845). Mothers whogive food in the bottle have a greater tendency to “maternal control”,i.e. the child has less control of their own intake, compared tobreastfed children (E. M. Taveras et al. Pediatrics, 2004, vol. 114 (5)e577-e584. and R. S. Gross et al. Academic Pediatrics, 2010; 10:29-35and L. Ruowei et al. Pediatrics, 2008; 122:S77-S85).

The effect of increased “maternal control” has been twofold: to providean accelerated rate of obesity for heavy children, but also increasingproblems with underweight children (C. Farrow & J. Blissett. Pediatrics,2006, vol. 118 (2) e293-e29). There are also some studies which haveshown that young infants are able to down, and up regulate food intake,respectively depending on the energy density of the infant formula (S.J. Fomon et al. J. Nutrition, 1969, 98: 241-254 and S. J. Fomon et al.Acta Paediatr Scand 64: 172-181, 1975).

The formula according to the invention comprises a low level of proteinand also a low level of total energy content.

Energy Density

The invented formula has an energy level of for example 67-58 kcal/100ml, or lower or for example lower than 60 kcal/100 ml or between 58-62kcal/100 ml or for example 58-60 kcal/100 ml. These selected energylevels are at the lowest level of the Commission Directive 2006/141/EC.In the report of the Scientific Committee on Food on the revision ofEssential Requirements of Infant formula and Follow-on Formula it issaid that “It should be emphasized that an energy intake below therecommended intake does not mean that individually this intake isdeficient and can be harmful for the subject.” The invented formula hasa lower energy density than conventional formulas and is nutritionalcomplete and fulfills the nutritional needs of a fast growing infantduring the first year of life.

Since a part of the total carbohydrates in breast milk (theoligosaccharides) is not used as an energy source and the lactosecontent in infant formula earlier was regarded as the same as the totalcarbohydrate content in breast milk, the content of lactose in theinvention formula is reduced in order to reach a nutritional compositionwith decreased energy density (kcal/100 ml).

Protein Content

Further, the formula according to the invention comprises a low level ofprotein, in g/100 ml, and still a low percentage of energy (E %) derivedfrom proteins compared to a standard formula. The nutritionalcomposition according to the invention comprises 7.2-8.4 E % protein,especially 7.8-8.4 E % protein or for example 8.0-8.3 E % protein.

The protein content of the ready to drink nutritional composition is forexample lower than 1.25 g/100 ml or for example lower than 1.25 g/100 mlor for example between 1.1-1.25 g/100 ml or between 1.1 g/100 ml tolower than 1.25 g/100 ml.

Fat Content

The invented formula further has a high E % (derived) from fat. The fatcontent of the nutritional composition according to the invention is atleast 49% or more of the total energy content of the nutritionalcomposition, for example, a fat content which is 49-54% or for example,50-54%, especially 52-53%, or for example 51.8-53.4% of the total energycontent of the nutritional composition.

Fat is necessary in the diet of infants and young children because oftheir extraordinary energy needs and limited dietary intake capacity. Inaddition, different fat sources provide poly unsaturated essential fattyacids as linoleic- and linolenic acids as well as long chain polyunsaturated essential fatty acids as arachidonic acid anddocosahexaenoic acid.

Deficiencies in the amounts of these long-chain poly unsaturated fattyacids in the diet during infancy may affect the maturation of thecentral nervous system, including visual development and intelligence(see for example E. E. Birch et al. Early Hum Dev, 2007, Vol. 83,279-284 and M. S. Kramer et al. Arch Gen Psychiatry, 2008;65(5):578-584).

The nutritional composition according to the invention further comprisesfor example 0.43-0.47% or for example 0.45% arachidonic acid (ARA) (n−620:4) and for example 0.26-0.30% or for example 0.28% docosahexaenoicacid (DHA)(n−3 22:6) of total fatty acids, respectively. To get thesefatty acids in these percents and ratios raw material from algal oil andfungal oil are used. Further the invention formula may comprise rapeseed oil, palm olein oil, sun flower oil and sun flower high oleic oilto get a fatty acid pattern similar to breast milk. The sun flower oilscontribute mainly with the essential fatty acid linoleic acid (n−618:2). And the rape seed oil contributes mainly with the essential fattyacid linolenic acid (n−3 18:3). Other oils which also may be used are:rape seed oil (high oleic), soybean-, maize-, safflower-, eveningprimrose-, borage-, palm-, palm olein-, palm kernel-, coconut-,babassu-, fish oil, egg lipids, structured fat with high percentpalmitic acid esterified to β-position in the triglycerides and lard. Inorder to even better mimic the fat composition in breast milk cream isused.

The use of dairy cream as an ingredient in the present nutritionalcomposition (or the use of dairy cream solids when making a nutritionalcomposition powder to be mixed with water) contributes to the highlevels of milk derived cholesterol in the nutritional compositionaccording to the invention. This dairy cream usage contributes to thehigh levels of cholesterol (5-10 mg/100 ml) in the composition accordingto the invention. Due to the special composition according to theinvention the addition of cholesterol as an ingredient (due to additionof dairy cream and whey protein concentrate rich in phospholipids) givesa similar blood cholesterol level as in breastfed infants during thefeeding period but also later in life for those infants fed with thenutritional composition according to the invention.

The cream also improves the taste of the invention formula. The formulaalso contains whey protein concentrate rich in phospholipids which alsocontribute to the content of milk derived cholesterol in the inventionformula as well as of the milk derived phospholipid sphingomyelin.Sphingomyelin is included in an amount of 10 mg/100 ml or higher. Theinvention formula comprises for example on dry basis between 26-32weight percent fat or for example on dry basis 30.7 weight percent fatwhereof between 15-19 weight percent of the total amount fat isvegetable fat, or for example 18.5 weight percent of total fat contentis vegetable fat.

The content of medium chain fatty acids (MCT) comprising 8 to 10 carbonsin the nutritional composition according to the invention is for example0.5-3 weight percent of total amount of fatty acids or for example 1-2weight percent of total amount fatty acids in the composition. Theinvention formula mimics the content of MCT in breast milk. Maturebreast milk has 1-2 weight percent MCT of total fatty acids (R. A.Gibson et al. Am. J. Clin. Nutr. 34: 252-257, 1981).

The use of sweet whey, cream and whey protein concentrate rich inphospholipids, during manufacturing of the nutritional composition orinfant formula according to the present invention, makes the nutritionalcomposition comprise a high amount of sialic acid and milk derivedphospholipids. The nutritional composition may for example comprise asialic acid content of 10 mg/100 ml or higher or 18 mg or higher or forexample a sialic acid content of between 10-25 mg/100 ml or between18-25 mg/100 ml. For example sweet whey solids, cream solids and wheyprotein concentrate solids rich in phospholipids may also be used toproduce a powder formula according to the invention which is intended tobe mixed with water before usage.

The use of these solids or ingredients also makes the nutritionalcomposition according to the invention to comprise lipid bound sialicacid as gangliosides of between 1.5-5% of total sialic acid content orfor example 4% of total sialic acid content. Said lipid bound sialicacid, as gangliosides, content in the formula according to the inventionis between o.03-0.08 weight percent of total fat content of the formulaor for example o.05 weight percent of total fat content of the formula.

Gangliosides stimulate intestinal maturation and support a healthy microflora and also the neuronal development and brain development. Sialicacid plays a role in cognitive development and can protect againstenteric infection.

Further the formula according to the invention comprises cholesterolwhich is a sterol that is mainly synthesized in the liver but also inother tissues. It is used to produce hormones in cell membranes and istransported in the blood plasma of all mammals. Breast milk comprisescholesterol. By using dairy cream and whey protein concentrate rich inphospholipids as raw material the invented formula's content is high incholesterol, similar to the level in breast milk.

The nutritional composition according to the invention has a cholesterolcontent of between 5-10 mg/100 ml, or between 7-10 mg/100 ml or forexample 8 mg/100 ml which for example is between 0.2-0.3 weight percentof the total fat content of the nutritional composition or for example0.23 weight percent of the total fat content of the nutritionalcomposition according to the invention.

Further sweet whey, cream and whey protein concentrate rich inphospholipids, all comprise cGMP. By, for example not removing cGMP fromthe nutritional composition according to the invention the sialic acidcontent is kept high. High sialic acid content is for example about10-25 mg/100 ml or between 18-20 mg/100 ml of the nutritionalcomposition according to the invention. By not removing cGMP from theraw materials used to produce the formula, the nutritional compositionaccording to the invention is likely to for example increase the levelof sialic acid in saliva (more similar to breastfed). The higher intakeof sialic acid can have an effect on for example morbidity and cognitivebehaviour in the invention formula-fed infants.

Sphingomyelin is the major component of the phospholipid fraction inbreast milk, and is found in lower concentrations in conventionalnutritional compositions compared to the formula according to theinvention. Sphingomyelin is metabolized to ceramide which concentrationcorrelates with degree of myelination of the nervous system. Experimentson rats with experimentally inhibited myelination have shown thatsupplements of sphingomyelin increases myelination (K. Oshida et al.Pediatr Res, 2003, vol. 53 (4) 589-593). The milk derived sphingomyelincontent in the formula according to the invention is 9 mg/100 ml orhigher, or between 9-15 mg/100 ml, or 13 mg/100 ml.

The nutritional composition according to the invention comprises aspecial composition of raw materials. The nutritional compositionaccording to the present invention still has a low burden-effect on themetabolic system of the formula-fed infant although it comprises cGMP.

The levels of arachidonic acid (ARA) and docosahexaenoic acid (DHA) inthe nutritional composition according to the invention are of similarlevels as present in breast milk.

The present invention provides a nutritional composition and a methodfor producing such a composition.

Non-Protein-Nitrogen

Non-protein nitrogen (NPN) is a term used to refer collectively tocomponents which are not proteins which are present in food and whichcomprise nitrogen. (NPN in milk is mainly urea-nitrogen (about 50%),creatine, creatinine, NH3 etc.)

Since it is important not to have a surplus of nitrogen in formulas forinfants we have endeavoured to have a low level of NPN<20 mg/100 ml inthe nutritional composition according to the invention, for example alow non-protein nitrogen (NPN) value between 0.015-0.020 g/100 ml.Surprisingly the invention formula has a low NPN value although it has atotal new composition of raw materials.

Amino Acid Profile

It is known that an infant formula needs a predetermined amino acidprofile to fulfill the children's need. This is also regulated by thegovernment Commission Directive 2006/141/EC. The amino acid supply in aninfant's first months of life must be sufficient in quantity as well asquality to fulfill the needs of this period of life. Guidelines,recommendations with minimum values have been established with regard toamino acid composition of infant formulas. An amino acid profile of thenutritional composition according to the invention is presented in thetable below. The clinical study confirms that the amino acid compositionin the invention formula is adequate for the requirement for growth.

Minimum value Interval according Commission Directive to the inventionAmino acid (mg/100 kcal) (mg/100 kcal) Leucine 166 197-229 or 217 Lysine113 165-192 or 180 Methionine 23 36-42 or 40 Cystine 38 40-46 or 44Phenylalanine 83 83-96 or 87 Tyrosine 76 64-74 or 72 Threonine 77114-132 or 124 Tryptophan 32 35-41 or 39 Valine 88 116-135 or 127Isoleucine 90 116-135 or 127 Histidine 40 46-53 or 50 Cystine +Methionine* 61 76-88 or 84 Phenylalanine + Tyrosine* 159 147-170 or 159

The concentration of methionine and cysteine can be calculated togethersince the amino acid cysteine can be formed from methionine. And theconcentration of tyrosine and phenylalanine can be calculated togethersince the amino acid tyrosine can be formed from phenylalanine.Therefore also combined levels of these amino acids are specified in thetable above*.

Amino Acid Sources of the Present Nutritional Composition:

The formula according to the invention has a composition which is suchthat the wanted amino acid profile is achieved without addition of anyfree amino acid. The formula according to the invention is manufacturedwithout addition of any free amino acid (or isolated amino acids) to geta desired amino acid profile.

The wording free amino acids or isolated amino acids in this applicationmean descriptions for an amino acid substance which is isolated as afree acid or as a salt.

The formula according to the present invention is therefore not enrichedwith isolated amino acids, for example free amino acids. This is anadvantage since free amino acids are usually bitter in taste. It is alsoexpensive to add amino acids in their pure form. By using theingredients according to the present invention the nutritionalcomposition according to the invention does not need further addition offree or isolated amino acids and is therefore more similar to breastmilk in taste.

Production Method

The formula according to the invention is according to one embodimentproduced by mixing the below ingredients in kg per 1000 kg nutritionalcomposition dry powder or kg per 8770 L finished nutritionalcomposition.

Interval in Amount in the the formula formula according to according tothe invention the invention (kg/1000 kg (kg/1000 kg dry dry powder orpowder or Raw material kg/8770 L) kg/8770 L) Sweet whey solids 32-40 36± 2  Sodium caseinate 4.6-5.7 5.2 ± 0.3 Skimmed milk solids 66-81 74 ±4  Whey protein concentrate 47-58 52 ± 3  solids (rich in phospholipids)Cream solids 117-143 130 ± 6  

The nutritional composition may further comprise vitamins, minerals,fats, lactose and/or other essential nutrients (for example choline,taurine, inositol, carnitine, nucleotides).

Further, the nutritional composition according to the invention maycomprise other ingredients as long as the specification of thenutritional composition, described above of the invention is fulfilled.

Whey Protein Concentrates Solids (Rich in Phospholipids)

Whey protein concentrate solids rich in phospholipids used as acomponent in the nutritional composition according to the invention is awhey protein concentrate with a high concentration of bioactive proteinsand lipids. The whey protein concentrate has a high nutritional value,and is applicable in infant and clinical nutrition. Whey proteinconcentrate solids rich in phospholipids contain most of the insolublemembrane protein fragments from MFGM originally present in the whey, inaddition to residual whey components, proteins, lactose and salts. Theinvention utilizes, whey protein concentrate solids rich inphospholipids obtained after removal of the major whey proteins by knownindustrial processing, such as filtration, ion-exchange chromatography,and the like. This fraction contains most of the insoluble membranefragments, which contain protein and associated fat. The whey proteinconcentrate solids rich in phospholipids contains bioactive compounds,such as lactoferrin, α-lactalbumin, butyrophilin, MUC1, PAS6/7(lactadherin), gangliosides, CD14, TLR1 and TLR4, IgG, cGMP, sialic acidand phospholipids (for example sphingomyelin, phosphatidyl choline,phosphatidyl serine and phosphatidyl ethanolamine). Phospholipids areimportant constituents of cellular membranes contributing significantlyto the membrane structure and function.

Lacprodan MFGM-10 (from Arla foods) or similar raw materials from othersuppliers may be used as enriched phospholipid whey protein concentratesolids in a formula according to the invention. For example the sourceof enriched phospholipid whey protein concentrate solids comprises atleast 20 wt % phospholipids based on total lipid content, for example 20to 70 wt % or for example 25 to 55 wt % phospholipids based on totallipid of the enriched phospholipid whey protein concentrate solidsource.

The whey protein concentrate solids rich in phospholipids used in thenutritional composition according to the present invention is notdepleted of cGMP.

The components of the whey protein concentrate solids rich inphospholipids may affect the development of the nervous system,morbidity and psychomotor development in a positive manner for infantsfed with the nutritional composition according to the invention comparedto infants fed standard infant formula or the control formula accordingto the invention.

Whey protein concentrate solids rich in phospholipids from bovine milkcontain unique polar lipids and membrane specific proteins, for examplelactoferrin, butyrophilin, MUC1 and PAS6/7 (lactadherin), CD14, TLR1 andTLR4 and phospholipids (including for example sphingomyelin andgangliosides). These components are recognized as nutritional andbioactive milk constituents and are present only scarcely in bovine milkcompared to human milk.

Whey protein concentrate solids comprise gangliosides, sialic acid,sphingomyelin, phosphatidyl serine, phosphatidyl choline, phosphatidylethanolamine, lactoferrin, α-lactalbumin, etc.

Sweet Whey

Sweet whey is rich in α-lactalbumin. The high α-lactalbumin contentmakes it ideally suited as a protein source in infant formulas in orderto fulfil desired amino acid pattern. Sweet whey also contains cGMPwhich is a source of sialic acid.

Cream

Cream is a natural and valuable source of short and medium chain fattyacids as well as milk derived cholesterol. The milk derivedphospholipids in cream are besides important nutritional substances alsovaluable emulsifiers. The formula according to the invention may bemanufactured using cream or cream solids. The fat content of the creamused according to the invention is for example of 36-40 wt % fat or 37wt % fat.

Caseinate

Sodium caseinate or partly other salts of caseinates may be used in theinvention formula.

Hydrolysed Protein

The protein source in the invention formula may be a hydrolysed protein.

Below is an exemplified description of the production process of theformula according to the invention, the following example of theinvention is not limiting the scope of the invention:

The present invention provides a ready to drink nutritional compositionor a powder formula intended to be reconstituted with water to a readyto drink nutritional composition and a method for producing suchcompositions.

In one embodiment the composition is a powder suitable for making aliquid composition after reconstitution with water. Or for example thecomposition is a ready to use liquid product.

Below is an example of ingredients for making the nutritionalcomposition according to the invention.

Example of amounts of ingredients (kg/1000 kg) of a dry powder formulaaccording to the invention which is intended to be reconstituted withwater before usage (amounts of ingredients for the a ready to drinkformula is below described in kg/8770 L);

Amount (interval) (kg/1000 kg or Description kg/8770 L)) Lactose 476-527Cream solids 123-136 Skim milk solids 70.0-77.3 Rape seed oil 51.6-57.0Palm olein oil 51.6-57.0 Whey protein concentrate solids rich in49.7-55.0 phospholipids Sun flower oil 38.3-42.3 Sweet whey solids34.5-38.1 Sun flower oil HO 24.9-27.6 Minerals 16.1-17.8 Sodiumcaseinate 4.92-5.44 Dry lecithin 4.26-4.70 Arachidonic acid oil1.60-3.50 Docosahexaenoic acid oil 1.60-2.17 Vitamin mix 1.29-1.43Choline, taurine, myo-inositol, L-carnitine 1.21-1.34

Examples of production methods according to the invention, not limitingthe scope of the invention;

Production method of a powder nutritional composition according to theinvention:

Milk based raw materials are mixed to a slurry. Standardized milk ormilk powder and liquid whey or whey powder are mixed, if necessary, withadditional water. Suitable equipment mixes the slurry in a tank withnegative pressure to reduce foaming and incorporation of air.

Emulsifier and fat soluble vitamins are added to a blend of vegetableoils. The fat phase is then incorporated in the milk phase either in themixing tank or dosed in line before homogenization. In line dosing ofoil means that a part of the milk phase is heated, oil is dosed into thestream, homogenized and cooled down again.

Water soluble vitamins, additives such as taurine and minerals with apro oxidative effect such as ferrous- and copper salts are added justbefore concentrating the slurry by means of a finisher to a final drymatter content of 50-55%. The concentrate is then heat treated to ensurethe microbiological quality, spray dried, the powder cooled and stored.After quality control, product is packed or, if it is a semi product,first blended, combining the spray dried semi product with additionalminerals, vitamins, bioactive ingredients and citric acid.

Production method of a Ready-to-drink nutritional composition accordingto the invention:

Water, made alkaline with calcium hydroxide, is mixed with whey or wheypowder. The solution is neutralized before adding the carbohydratesource and standardized milk. Additional ingredients such as choline,taurine, inositol and carnitine are added before pasteurisation and fatphase injection and homogenization. The fat phase is made up ofvegetable oils, emulsifiers and fat soluble vitamins. Beforesterilization, vitamins are added and quality check is performed. Theproduct is UHT-treated, a quick heat treatment at about 140° C. for 5seconds, cooled and aseptically packed.

(UHT means Ultra High Temperature. Products from an UHT-process havegood keeping qualities with retained nutritional values).

Below is an example of the nutritional composition according to theinvention and also a description of a control formula, both used in acomparative study. The below example of the invention is not limiting tothe scope of the invention;

The infant formula (Formula A) used in the study is an example of anutritional composition according to the invention. The Control Formulais used for comparison. The comparative Control Formula is arepresentative infant formula of good quality available on the market.

The formulas included in the study have the following compositions (seetable below)—Formula A is an example of the nutritional compositionaccording to the invention;

Formula A Control Formula Description (kg/1000 kg) (kg/1000 kg) Lactose502 536 Cream solids 130 89.6 Skim milk solids 73.7 105 Rape seed oil54.3 43.4 Palm olein oil 54.3 75.9 Whey protein concentrate solids 52.4(rich in phospholipids) Sun flower oil 40.3 30.7 Sweet whey solids 36.361.1 Sun flower oil HO 26.3 30.7 Minerals 17.0 10.1 Sodium caseinate5.18 6.56 Dry lecithin 4.48 4.03 Arachidonic acid oil 3.33 2.91Docosahexaenoic acid oil 2.07 1.80 Vitamin mix 1.38 1.48 Choline,taurine, myo-inositol, 1.27 1.04 L-carnitine L-arginine 0.689 Potassiumcitrate 4.68 2.58 Calcium carbonate 3.33 3.33 Potassium chloride 3.082.19 Calcium hydrogenphosphate 1.94 Magnesium sulphate 1.78 0.583 Sodiumchloride 1.40 0.972 Ascorbic acid 1.08 1.22 Choline chloride 0.648 0.486Sodium citrate 0.500 Taurine 0.415 0.370 Ferrous sulphate 0.178 0.150myo-Inositol 0.135 0.120 Zinc sulphate 0.0863 0.0769 Ascorbyl palmitate0.0782 0.0751 L-carnitine 0.0756 0.0656 Vitamin D3 0.0539 0.0480 VitaminA 0.0476 0.0424 DL-a-tocopherol 0.0350 0.0362 Calcium D-pantothenate0.0296 0.0263 Niacin 0.0180 0.0160 Copper sulphate 0.00846 0.00754Thiamine hydrochloride 0.00676 0.00602 Vitamin K1 0.00561 0.00500Pyridoxine hydrochloride 0.00546 0.00486 Potassium iodide 0.000730.00073 Folic acid 0.00062 0.00055 Sodium selenite 0.00039 0.00039Biotin 0.00011 0.00010

Formula A, which is a nutritional composition according to theinvention, with the ingredients described above, comprises thenutritional values presented below as ready for consumption (114 g ofpowder formula A is mixed with 900 ml water which gives 1000 ml ready todrink product);

-   -   a total energy content of 60 kcal/100 ml,    -   a protein content of 1.2 g/100 ml,    -   an energy content from protein of 8.0 (E %) of the total energy        content of the nutritional composition    -   a protein:energy ratio of 2.0/100 kcal    -   a fat content which is 52.5 (E %) of the total energy content of        the nutritional composition according to Formula A    -   a medium chain fatty acid (comprising 8 to 10 carbons) content        of 1.6 wt % of total amount of fatty acids in Formula A    -   sialic acid content of 19 mg/100 ml    -   a cholesterol content of 8 mg/100 ml    -   lipid bound sialic acid as gangliosides of 4 wt % of total        sialic acid content    -   sphingomyelin content of 13 mg/100 ml

Formula A has a high content of sialic acid from natural sourcescompared to standard formulas. The sialic acid content comes from twodifferent sources, one, fromwhey protein concentrate solids (rich inphospholipids), which is lipid bound and the other from GMP, which isbound to carbohydrates. Formula A has a high milk derived content ofsphingomyelin from natural sources compared to the Control Formula,namely whey protein concentrate solids (rich in phospholipids). It is anadvantage to use said natural sources of sialic acid and sphingomyelin.

Energy % (E %) is a normal way to express the amount of kcal, whichcomes from fat, protein and carbohydrates in a nutritional formulation.The National food agency in Sweden (Livsmedelsverket) has identifiedthis on http.//www.slv.se/sv/gruppl/Mat-ochnaring/Svenska-narings-rekommendationer/Kalorier-kilojoule-ochenergiprocent---hur raknar-man/

The control formula, with the ingredients described in the table above,comprises the nutritional values presented below as ready forconsumption (130 g of powder control formula is mixed with 900 ml watergives 1000 ml ready to drink product);

-   -   a total energy content of 66 kcal/100 ml    -   a protein content of 1.27 g/100 ml,    -   an energy content from protein of 7.7 (E %) of the total energy        content of the nutritional composition according to the control        formula    -   a fat content of 44.7 (E %) of the total energy content of the        nutritional composition according to the control formula    -   a medium chain fatty acid (comprising 8 to 10 carbons) content        of 1.5 wt % of total amount of fatty acids in the control        formula    -   sialic acid content of 16 mg/100 ml    -   a cholesterol content of 4 mg/100 ml    -   lipid bound sialic acid as gangliosides of 2 wt % of total        sialic acid content according to the control formula    -   sphingomyelin 1.8 mg

Study

Study Design

The study is a randomized double-blind intervention trial withexclusively breastfed infants as a reference group which means thatthree groups of children participate in the study:

1) Children who are breastfed.

2) Children who receive modified infant formula, “Formula A”, accordingto the invention (see description above).

3) Children who receive a representative infant formula of good quality,herein called “Control Formula” (see description above)

Group Size

The study was set up to detect a possible difference of 0.5 standarddeviation (SD) for each outcome variable, which corresponds to a weightdifference of about 0.4 kg at 6 months or a difference of 3.25 percentof body fat measured by plethysmography at 2 months of age. The visualacuity equivalent to 0.5 SD is 0.25 octaves at 4 months of age, which isthe difference seen when compared to children with feeding with orwithout DHA supplement. With a statistical “power” of 80% a group sizeof just over 60 children is required. 80 children were recruited pergroup, which gave a sufficient number of children per group completingthe study.

Infants Included in the Study

From March 2008 to February 2012, 160 formula-fed infants (80 girls and80 boys) and a breast-fed reference (BFR) group with 80 infants (40girls and 40 boys), all born at Umea University Hospital, Umea, Sweden,were recruited after inviting parents by telephone. Inclusion criteriawere <2 months of age, gestational age at birth 37-42 weeks, birthweight 2500-4500 g, absence of chronic illness, and exclusiveformula-feeding or, for the BFR group, exclusive breastfeeding atinclusion and mother's intention to exclusively breastfeed until 6months. Formula-fed infants were stratified for sex and randomized toreceive a low energy, low protein experimental formula (Formula A) or astandard formula (Control Formula) from inclusion until 6 months of age.Twins were co-randomized to the same intervention group. Theintervention was blinded both to parents and staff until all infants hadfinished the intervention. Powdered formula was distributed to familiestogether with preparation instructions in identical boxes marked with acode number.

Exclusion Criterion

Children with chronic diseases that may affect the outcome variables,such as neurological, endocrine or mal absorption illness are excludedfrom the study. Even children who for various reasons are not able tocomplete the study will be monitored and included in the statisticalanalysis according to the “intention to treat”.

Outcome Parameters

The children will be followed from the time of enrollment up to 1 yearof age with blood, saliva and stool samples and other tests, see below.The study is divided in two parts. The first study part is frominclusion up to 12 months of age, and the second part of the study is at5 years of age.

Assessment of Growth

Visits were made at baseline (<2 months), 4 months and 6 months. At eachvisit, weight (Seca 757, Seca, Hamburg, Germany), length (Seca 416,Seca, Hamburg, Germany) and head circumference (Seca 212, Seca, Hamburg,Germany) were measured. Weight was recorded with an accuracy of 5 grams,length and head circumference with an accuracy of 0.1 cm. At inclusionand 4 months, body composition was measured using air-displacementplethysmography (PeaPod©, Life Measurement Inc, Concord, Calif., USA).Age-adjusted z-scores for weight, length, head circumference and bodymass index (BMI) were calculated using the WHO growth standards.

Blood Samples and Analyses

At each visit, venous blood samples were drawn >2 h after the latestmeal. From each group (FA, CF and BF), samples from 20 randomly selectedinfants (10 girls and 10 boys) were analyzed for plasma amino acidpattern. After acidifying plasma samples with sulfosalicylic acid,centrifuging and diluting the supernatant with Li-diluent spiked withAE-Cys, amino acids were separated by ion-exchange chromatographyfollowed by analysis with a ninhydrin reaction detection system (HitachiL-8900 Amino Acid Analyzer).

Apo A1, apo B, cholesterol, HDL and triglycerides were analysed withVitros Chemistry ApoAl reagent, ApoB reagent, CHOL slides, dHDL slidesand TRIG slides on Vitros 5.1 FS (Ortho Clinical Diagnostics Inc). LDLwas estimated by Friedewald's formula (Friedewald, W. T. et alEstimation of the concentration of low-density lipoprotein cholesterolin plasma, without use of the preparative ultracentrifuge. Clin Chem,1972, 18, (6): p 499-502).

Metabolomics

Metabolomics was studied in the metabolites resulting from cellularmetabolism. Metabolomics was used in order to detect specific metabolicdifferences between breastfed and formula-fed infants as well as betweenformula fed infants.

Development

The neurologic development can be measured with greater accuracy, theolder the child is. At 12 months a psychologist performed a test withBayley Scales of Infant and Toddler Development-III.

By the age of 5 years again a cognitive testing will be done, this timewith the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R).

Dietary Record

Each month, starting from baseline, parents or caregivers record thetype and amount of each food item consumed by the infant during 3consecutive days up to 6 months of age.

Statistics

All analyses are presented on an intention-to-treat basis. Statisticalcalculations were made using IBM SPSS Statistics Version 19 (©IBM 1989,2010). Comparisons of proportions were made by chi-square test or, whenthe expected count in any cell was less than 5, by Fisher's exact test.Comparisons of means were made by independent samples t-test. Variablesthat were not normally distributed were log-transformed beforecalculations and transformed back for presentation as geometric meansand 95% confidence intervals. Adjusted p-values for differences betweenthe Formula A and Control Formula groups were calculated in amultivariate model, including those background variables thatsignificantly differed between the groups. Differences in levels ofamino acids were calculated with ANOVA, and compensated for multiplecomparisons by Bonferroni post-hoc test.

Results

The growth between the breast fed infants and the Formula A fed infantsdid not differ. The new nutritional composition according to theinvention reduces the differences between breastfed and formula-fedinfants in terms of metabolic factors, as well as neurologicaldevelopment.

Growth

There were no differences in age-adjusted z-scores for weight (FIG. 1 ),length (FIG. 2 ), head circumference (FIG. 3 ) or body mass index (FIG.4 ), between the Formula A group and the breast fed group or between theFormula A and the control formula group up to 6 months of age.

In earlier studies it is consistently shown that the weight at a certainage is higher for formula fed infants compared to breast fed infants.

Nor were there differences in body fat % between the Formula A and thebreast fed group or the Formula A and the Control Formula groups, cfTable 1.

TABLE 1 p (adjusted p BF Control Breast p ¹) vs Formula formula fed FAvs FA + A (FA) (CF) (BF) CF CF Body composition (% fat) Baseline 20.6 ±4.5 21.2 ± 4.3 21.6 ± 4.1 0.43 (0.22) 0.26 4 months 26.4 ± 4.4 26.3 ±4.7 26.5 ± 3.9 0.91 (0.68) 0.78 ¹ = adjusted for weight gain duringpregnancy, gestational diabetes, parental BMI and age at inclusion

Plasma Amino Acid Levels

The levels of the plasma amino acids were within a satisfied range table2 and show that the lower level of protein per 100 ml fulfil the need ofa growing infant. Normally tryptophane is the limiting amino acid ininfant formula. However, it was shown that the plasma level oftryptophane in this study was not different between the Formula A groupand the breast fed group.

Although the Formula A contains cGMP, which has a higher level ofthreonine, the results show that the plasma level of threonine inFormula A fed infants was in an accepted range.

TABLE 2 Mean levels of plasma amino acids in Formula A (FA), controlformula (CF) and breast-fed (BF) groups (μmol/ml), n = 20 in each group.Baseline 4 months 6 months FA CF BF FA CF BF FA CF BF EssentialIsoleucine  0.76^(ab) 0.84^(a) 0.66^(b) 0.74^(a) 0.90^(b) 0.66^(a) 0.76^(a)  0.74^(ab) 0.61^(b) Leucine  0.121 0.130 0.122  0.111  0.1300.113  0.119^(a)   0.110^(ab) 0.097^(b) Lysine  0.21^(ab) 0.22^(a)0.18^(b) 0.19^(a) 0.20^(a) 0.16^(b)  0.17^(a)  0.17^(a) 0.14^(b)Methionine  0.031^(a) 0.032^(a) 0.025^(b)  0.025^(a)  0.025^(a)0.018^(b)  0.019  0.018 0.016 Phenylalanine   0.057^(ab) 0.060^(a)0.051^(b)   0.053^(ab)  0.057^(a) 0.050^(b)  0.056  0.057 0.052Threonine 0.23 0.25 0.14 0.20^(a) 0.22^(a) 0.14^(b)  0.17^(a)  0.18^(a)0.13^(b) Tryptophan  0.123 0.094 0.114  0.089  0.110 0.098  0.096  0.0950.081 Valine  0.21^(a) 0.22^(a) 0.17^(b) 0.19^(a) 0.22^(b) 0.17^(a) 0.21^(a)  0.20^(ab) 0.17^(b) Non-essential Alanine 0.40 0.45 0.360.40^(a) 0.44^(b) 0.39^(a) 0.38 0.38 0.35 Arginine 0.68 0.83 0.81 0.79 0.90  0.82 0.78 0.95 0.76 Asparagine 0.26 0.54 0.22  0.29^(ab) 0.32^(a)0.24^(b) 0.26 0.24 0.21 Aspartic  0.29^(ab) 0.33^(a) 0.24^(b) 0.23^(a)0.28^(b) 0.22^(a)  0.23^(ab)  0.28^(a) 0.22^(b) Glutamic  0.44^(a)0.45^(a) 0.55^(b) 0.34^(a)  0.36^(ab) 0.40^(b)  0.31^(a)  0.32^(ab)0.37^(b) Glutamine 0.24 0.20 0.21 0.46  0.42  0.49 0.43 0.38 0.37Glycine 0.25 0.25 0.23 0.23  0.22  0.21 0.22 0.21 0.19 Histidine  0.1010.099 0.094  0.089  0.092 0.088  0.086  0.081 0.085 Proline 0.20 0.230.20 0.17^(a) 0.22^(b) 0.22^(b) 0.18 0.21 0.20 Serine 0.15 0.17 0.160.16  0.17  0.18 0.14 0.15 0.14 Tyrosine  0.088 0.091 0.090  0.083 0.082 0.076  0.080^(a)   0.076^(ab) 0.062^(b)

Statistical test with ANOVA (IBM SPSS Statistics 19), differences areconsidered significant at a level of p<0.05 after Bonferroni post hoctest for multiple comparisons (^(a) differs from ^(b)).

Cognitive Performance

In the preliminary analysis, 70, 64 and 71 infants have been tested withBayley Scales of Infant and Toddler Development-III at 12 months in theFormula A, Control Formula and breast fed groups, respectively. It wasfound that infants fed the Formula A had a higher cognitive score at 12months compared to infants fed the Control Formula, table 3. The FormulaA fed infants had a cognitive score similar to the breast fed infants.The magnitude of the difference between the groups is well in line witha meta-analysis of studies on cognitive function in formula fed comparedto breast fed infants This implies that one or several factors inFormula A are needed for optimal cognitive development and that thosefactors can reduce the differences in cognitive function observedbetween breast-fed and formula-fed infants.

TABLE 3 Bayley-III composite score (mean ± SD) at 12 months for theFormula A (FA), Control formula (CF) and breast fed (BF) groups. p-valuep-value (FA vs (FA vs FA CF BF CF) BF) Cognitive 105.9 ± 9.2  101.8 ±8.0  106.4 ± 9.5 0.007 0.73 Motor 98.7 ± 9.3 98.2 ± 9.0 100.2 ± 7.2 0.760.25 Verbal 102.6 ± 10.5 102.5 ± 8.9   106.7 ± 10.7 0.92 0.022

Blood Lipids

There were differences in blood lipids between the Formula A and ControlFormula groups. The Formula A contained a higher level of cholesterolthan the Control formula which also resulted in higher level of plasmacholesterol in Formula A fed infants which also was similar to thebreast fed group. Longer follow-up is needed, to have more clearinterpretations on programming effects of this early intervention onfuture risk for cardiovascular disease. There are no differences inplasma triglycerides levels between Formula A, Control Formula andbreast fed groups.

Cholesterol

Both the Formula A and the Control Formula used in the study contained ahigher than normal level of cholesterol. The control formula 40 mg/l andthe Formula A 80 mg/l. The cholesterol level in breast milk is oftensaid to contain about 120 mg/l, but is dependant of many factors. Moststandard infant formula contains less than 10 mg/of cholesterol.

The cholesterol level in the Formula A was increased by using a recipecontaining milk cream, milk protein fractions containing MFGM (milk fatglobule membrane) and other milk protein fractions containingcholesterol. The acquired level of cholesterol, 80 mg/l, has previouslyonly been reached by adding pure cholesterol, lard or egg preparations.

The control formula used in this study contained 40 mg/l of cholesterol.The recipe used contained milk cream and some milk protein preparationsthat contained cholesterol.

In previous performed studies breast fed infants have a higher plasmacholesterol level than formula fed infants. This is especially seenduring the first 6 months of life. After that there is a diminisheddifference in plasma cholesterol levels between breast fed and formulafed infants.

The results from this study show that, by increasing the cholesterollevel in the Formula A by incorporating various cholesterol containingmilk products into the product, we have managed to reach a plasmacholesterol level at 6 months similar to the group that was breast fed.Breast fed 2.20 plus/minus 0.55 and Formula A group 1.99 plus/minus0.55. This was achieved in spite of a much lower base line plasmacholesterol level in the Formula A group in comparison with the breastfed group. These differences in the base line levels might be due tothat the infants in this group, before entering the study had consumedan infant formula with a low level of cholesterol.

The infants, who consumed the control formula did not reach a plasmacholesterol at 6 months, similar to the breast fed group. However it isimportant to observe that the control formula used in this studycontained higher level of cholesterol than most formula on the market.

Breast fed infants had a higher ratio of LDL/HDL than both infantformula groups at 6 months. But this difference was already seen at thebaseline. There was no difference between the groups regarding plasmatri glyceride levels.

Other Metabolic Parameters

Plasma analyses show that important metabolic compounds such asmyo-inositol in formula A fed infants were similar to breast fedinfants, but significantly different from control formula fed infants.

Dietary Intake

The finding in the present study that energy intake regulation offormula-fed infants occur even at a modest (9%) difference in energydensity, has not been shown previously. It can be concluded that infantsfed with Formula A had a growth similar to breast fed infants.

CONCLUSION

Although the Formula A had a lower energy content and lower proteincontent per 100 ml, than the control formula (CF), which represents astandard formula of high quality, the results show that the compositionof the Formula A fulfil the requirements for growth and body compositionof an Formula A fed infant in the same way as breastfed infants. Therewere no differences in age—adjusted z-scores for weight, height,head-circumference or BMI between the Formula A and the breast fedgroups or between the Formula A and the Control formula fed groups. Norwere there differences in body fat % between the Formula A and thebreast fed groups or the Formula A and the Control formula fed groups.The Formula A with its low protein level also met the requirements foradequate growth and metabolism of infants.

Further the results from this study show that, by increasing thecholesterol level in the Formula A, by incorporating various cholesterolcontaining milk products into the product, we have managed to reach aplasma cholesterol level at 6 months substantially the same as for thegroup that was breast fed.

It was also found that infants fed the Formula A had a higher cognitivescore at 12 months compared to infants fed the Control Formula. TheFormula A fed infants had a cognitive score similar to the breast fedinfants. The magnitude of the difference between the Formula A and theControl Formula groups is well in line with a meta-analysis of studieson cognitive function in formula fed compared to breast fed infants.This implies that one or several factors in Formula A are needed foroptimal cognitive development and that those factors can reduce thedifferences in cognitive function observed between breast-fed andformula-fed infants.

Further this study showed that the maternal control effect, which hasbeen seen earlier in studies, did not affect the intake of energy in thestudy infants, on the contrary the infants were able to regulate theintake of the volume of the formula and thus also the energy intake fromboth Formula A as well as from the Control Formula in order to growsimilar as breast fed infants.

1-27. (canceled)
 28. A nutritional composition, as a ready-to-useproduct or a ready-to-use product reconstituted with water from amanufactured powder, wherein the total energy content is 67 kcal/100 mlor lower and the composition comprises; a protein content which is 1.25g/100 ml or lower, an energy content from protein of 7.2-8.4 percentageof the total energy content of the nutritional composition, an energycontent from fat which is at least 49 percentage or more of the totalenergy content of the nutritional composition, a medium chain fatty acidcontent comprising 8 to 10 carbons which is less than 3 weight % oftotal amount of fatty acids, a sialic acid content of 10-25 mg/100 ml orhigher, a cholesterol content of 5-10 mg/100 ml. a sphingomyelin contentof 9-15 mg/100 ml.
 29. A method of treatment comprising administering toa subject in need thereof a nutritional composition according to claim 1as an nutritional composition for achieving a development and/or growthpattern and/or morbidity more similar to breast-fed infants and/orregarding parameters which is any of growth, body composition wt % fat,cholesterol level, blood urea nitrogen (BUN), sialic acid in saliva,fasting insulin levels or decreased risk for obesity in childhood,insulin resistance, total thickness of intimate and media of the vesselwall of carotid communis, inflammation parameters, microbiologicalparameters, plasma amino acids, IGF-1, dietary intake.
 30. A method forproducing a nutritional composition, comprising the steps; providingingredients per 1000 kg dry powder or per 8770 L ready to drinknutritional composition comprising; sweet whey solids between 32-40kg/1000 kg dry powder composition or per 8770 L ready to drinknutritional composition; sodium caseinate between 4.6-5.7 kg/1000 kg drypowder composition or per 8770 L ready to drink nutritional composition;skim milk solids between 66-81 kg/1000 kg dry powder composition or per8770 L ready to drink nutritional composition; whey protein concentratesolids rich in phospholipids between 47-58 kg/1000 kg dry powdercomposition or per 8770 L ready to drink nutritional composition; creamsolids between 117-143 kg/1000 kg dry powder composition or per 8770 Lready to drink nutritional composition; and mixing the ingredients.